Current and Advanced Applications of Gadoxetic Acid-enhanced MRI in Hepatobiliary Disorders.

Gadoxetic acid is an MRI contrast agent that has specific applications in the study of hepatobiliary disease. After being distributed in the vascular and extravascular spaces during the dynamic phase, gadoxetic acid is progressively taken up by hepatocytes and excreted to the bile ducts during the hepatobiliary phase. The information derived from the enhancement characteristics during dynamic and hepatobiliary phases is particularly relevant in the detection and characterization of focal liver lesions and in the evaluation of the structure and function of the liver and biliary system. The use of new MRI sequences and advanced imaging techniques (eg, relaxometry, multiparametric imaging, and analysis of heterogeneity), the introduction of artificial intelligence, and the development of biomarkers and radiomic and radiogenomic tools based on gadoxetic acid-enhanced MRI findings will play an important role in the future in assessing liver function, chronic liver disease, and focal liver lesions; in studying biliary pathologic conditions; and in predicting treatment responses and prognosis. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review.

DESCRIPTION: The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. METHODS: The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.

Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS: The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

Application of Artificial Intelligence for Diagnosis and Risk Stratification in NAFLD and NASH: The State of the Art.

The diagnosis of nonalcoholic fatty liver disease and associated fibrosis is challenging given the lack of signs, symptoms and nonexistent diagnostic test. Furthermore, follow up and treatment decisions become complicated with a lack of a simple reproducible method to follow these patients longitudinally. Liver biopsy is the current standard to detect, risk stratify and monitor individuals with nonalcoholic fatty liver disease. However, this method is an unrealistic option in a population that affects about one in three to four individuals worldwide. There is an urgency to develop innovative methods to facilitate management at key points in an individual's journey with nonalcoholic fatty liver disease fibrosis. Artificial intelligence is an exciting field that has the potential to achieve this. In this review, we highlight applications of artificial intelligence by leveraging our current knowledge of nonalcoholic fatty liver disease to diagnose and risk stratify NASH phenotypes.

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Calcium is the most abundant extracellular cation in the body, and it is responsible for structural and enzymatic functions. Calcium homeostasis is regulated by 3 factors: calcitonin, vitamin D, and parathyroid hormone (PTH). Hypercalcemia is defined by a serum calcium concentration >10.5 mg/dL, and it is classified into mild, moderate, and severe, depending on calcium values. Most cases are caused by primary hyperparathyroidism and malignancies. Various mechanisms are involved in the pathophysiology of hypercalcemia, such as excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion. The initial approach is similar in most cases, but a definitive treatment depends on etiology, that is why etiological investigation is mandatory in all cases. The majority of patients are asymptomatic and diagnosed during routine exams; only a small percentage of patients present with severe manifestations which can affect neurological, muscular, gastrointestinal, renal, and cardiovascular systems. Clinical manifestations are related to calcium levels, with higher values leading to more pronounced symptoms. Critically ill patients should receive treatment as soon as diagnosis is made. Initial treatment involves vigorous intravenous hydration and drugs to reduce bone resorption such as bisphosphonates and, more recently, denosumab, in refractory cases; also, corticosteroids and calcitonin can be used in specific cases. This review aims to provide a clinical update on current concepts of the pathophysiology of calcium homeostasis, epidemiology, screening, clinical presentation, diagnosis, and management of hypercalcemia.

Nutrient Drinking Test as Biomarker in Functional Dyspepsia.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent condition with multifactorial pathophysiology, including impaired gastric accommodation (GA), hypersensitivity to gastric distention, and delayed gastric emptying. Drink tests (DT) have been proposed as a potential biomarker for the presence and severity of gastric sensorimotor dysfunction. Thus, we aimed to summarize the state of knowledge on different DT and their potential as a biomarker for FD. METHODS: A PubMed and MEDLINE search was conducted for English language articles, reviews, meta-analyses, case series, and randomized controlled trials, including also published meeting abstracts. RESULTS: Several DT have been described in literature (e.g., different type of liquid, number of calories used, pace of drinking, and subject's awareness of the amount of liquid drunk). FD patients ingest significantly less volume in the different variants of the tests. The slow nutrient ("satiety drinking") test (SDT) studies show the most consistent separation between health and FD and correlation with GA. However, sensitivity to distention may be correlated with rapid DT. SDTs were used to evaluate the effect of several pharmacological agents, often showing concordance between their effects on GA and tolerated nutrient volume. This correlation was not found mainly for agents with central actions. DISCUSSION: An SDT is a potential diagnostic biomarker in FD, reflecting GA. Additional studies are required to confirm its role as a predictive biomarker for treatment outcome in FD.

Integrative Effects and Vagal Mechanisms of Transcutaneous Electrical Acustimulation on Gastroesophageal Motility in Patients With Gastroesophageal Reflux Disease.

INTRODUCTION: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003). DISCUSSION: The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism.

Noninvasive early diagnosis of intestinal diseases based on artificial intelligence in genomics and microbiome.

The maturing development in artificial intelligence (AI) and genomics has propelled the advances in intestinal diseases including intestinal cancer, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). On the other hand, colorectal cancer is the second most deadly and the third most common type of cancer in the world according to GLOBOCAN 2020 data. The mechanisms behind IBD and IBS are still speculative. The conventional methods to identify colorectal cancer, IBD, and IBS are based on endoscopy or colonoscopy to identify lesions. However, it is invasive, demanding, and time-consuming for early-stage intestinal diseases. To address those problems, new strategies based on blood and/or human microbiome in gut, colon, or even feces were developed; those methods took advantage of high-throughput sequencing and machine learning approaches. In this review, we summarize the recent research and methods to diagnose intestinal diseases with machine learning technologies based on cell-free DNA and microbiome data generated by amplicon sequencing or whole-genome sequencing. Those methods play an important role in not only intestinal disease diagnosis but also therapy development in the near future.

Functional dyspepsia in children: A study of pathophysiological factors.

BACKGROUND AND AIM: Functional dyspepsia (FD) is common in children, and treatment targeted towards the altered pathophysiology can improve outcome. We evaluated FD children for abnormality of gastric accommodation and emptying, psychological stressors (PS), Helicobacter pylori (HP) infection, and post-infectious FD. METHODS: Diagnosis of FD was based on ROME III criteria. Clinical evaluation including dyspeptic symptom scoring and assessment for PS was performed. Satiety drink test for gastric accommodation, gastroscopy with biopsy for HP infection, and solid meal gastric emptying were performed. Sixty-seven healthy children were enrolled for assessing PS and satiety drink test. RESULTS: Fifty-five FD children (33 boys, age 12 [6-18] years) with symptoms for 4 (2-48) months and dyspeptic score of 5 (1-13) were enrolled. PS were more common in FD than in controls (46/55 vs 9/67; P < 0.001). Median satiety drink volume was 360 mL (180-1320 mL); no patients had satiety drink volume of < 5th centile of healthy children. The frequency (98% vs 85%; P = 0.01) and severity (65 [10-175] vs 50 [5-130]; P < 0.001) of postprandial symptoms were higher in FD than in controls. Of the postprandial symptoms, pain (20.3% vs 0%; P = 0.000) was present only in FD. Delayed gastric emptying was present in 6.5%, HP infection in 11%, and post-infectious FD in 13% cases. Etiological factor was identified in 87% children, with 20% having multiple factors. CONCLUSIONS: Abnormality of gastric sensorimotor function is seen in one-fourth of FD cases. HP infection and post-infectious FD are present in 11% and 13% cases, respectively.

Qualitative diagnostic signature for pancreatic ductal adenocarcinoma based on the within-sample relative expression orderings.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancer, which is one of the most aggressive malignant neoplasms with a 9.3% five-year survival rate. The pathological biopsy is the current golden standard for confirming suspicious lesions of PDAC, but it is not entirely reliable because of the insufficient sampling amount and inaccurate sampling location. Therefore, developing a robust signature to aid the accurate diagnosis of PDAC is critical. METHODS: Based on the within-sample relative expression orderings of gene pairs, we identified a qualitative signature to discriminate both PDAC and adjacent samples from both chronic pancreatitis and normal samples in the training datasets and validated it in other independent datasets produced by different laboratories with different measuring platforms. RESULTS: A six-gene-pair signature was identified in the training data and validated in eight independent datasets. For surgical samples, 96.63% of 356 PDAC tissues, 100% of 11 pancreatitis tissues of non-cancer patients, and 23 of 24 normal pancreatic tissues were correctly classified. Especially, 59 of 60 cancer-adjacent normal tissues of PDAC patients were correctly identified as PDAC. For biopsy samples, all of 11 PDAC biopsy tissues were correctly classified as PDAC. CONCLUSION: The signature can distinguish both PDAC and PDAC-adjacent normal tissues from both chronic pancreatitis and normal tissues of non-cancer patients even when the sampling locations are inaccurate, which can aid the diagnosis of PDAC.

A novel discriminant formula for the prompt diagnosis of strangulated bowel obstruction.

PURPOSES: The diagnosis of strangulated bowel obstruction (SBO) is sometimes difficult. We attempted to create and verify a discriminant formula for use as a diagnostic aid for the early diagnosis of SBO. METHODS: This retrospective study included 97 patients who underwent an operation for SBO from January 2007 to September 2018. First, a discriminant analysis was performed for 73 patients who underwent an operation from January 2007 to December 2015 in order to obtain a formula. Next, we analyzed 34 patients who underwent an operation from January 2016 to September 2018 to verify the formula. RESULTS: The risk factors for SBO included ascites, signs of preperitoneal irritation, and lactate > 1.16 mmol/L. The discriminant formula is as follows: 1.954 × collection of ascites (1 or 0) + 1.239 × peritoneal irritation sign (1 or 0) + 0.378 × lactate - 2.331 (1: positive, 0: negative). The predictive value was as follows: sensitivity, 87.5%; specificity, 64.7%; and predictive accuracy, 73.5%. In patients who presented within 24 h of the onset, the sensitivity was 92.3%, the specificity was 75.0%, and the predictive accuracy was 85.7%. CONCLUSION: Our discriminant formula seems useful for the rapid diagnosis of SBO.

Laparoscopic ventral rectopexy using the transanal vacuum test for complete rectal prolapse.

Laparoscopic ventral rectopexy was performed in 84 patients with complete rectal prolapse from January 2016 to December 2019. In the initial 27 cases, three cases had recurrence, especially in cases of a long rectal prolapse measuring over 10 cm. In order to avoid recurrence, the transanal vacuum test was performed following the dissection of the rectovaginal septum towards the pelvic floor. The disappearance of rectal prolapse is confirmed by the intraoperative transanal vacuum test. When the posterior wall of the rectum showed the presence of prolapse according to the transanal vacuum test, then laparoscopic ventral rectopexy was converted to laparoscopic posterior rectopexy. In 94 cases in which laparoscopic ventral rectopexy was attempted, laparoscopic ventral rectopexy was completed in 57 cases, while the procedure was converted to laparoscopic posterior rectopexy in 37 cases. The recurrence rate following laparoscopic ventral rectopexy decreased from 11.1% (3/27) to 1.7% (1/57) after beginning to use the transanal vacuum test. Laparoscopic ventral rectopexy using the transanal vacuum test is therefore considered to be a useful technique to reduce postoperative recurrence.

The management of adult patients with severe chronic small intestinal dysmotility.

Adult patients with severe chronic small intestinal dysmotility are not uncommon and can be difficult to manage. This guideline gives an outline of how to make the diagnosis. It discusses factors which contribute to or cause a picture of severe chronic intestinal dysmotility (eg, obstruction, functional gastrointestinal disorders, drugs, psychosocial issues and malnutrition). It gives management guidelines for patients with an enteric myopathy or neuropathy including the use of enteral and parenteral nutrition.

AGA Technical Review on the Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D).

BACKGROUND & AIMS: The evaluation of patients with chronic watery diarrhea represents a diagnostic challenge for clinicians because organic causes, including inflammatory bowel disease, microscopic colitis, and chronic infection, must be differentiated from functional diarrhea and diarrhea-predominant irritable bowel syndrome. The purpose of this review is to summarize the available evidence on the usefulness of diagnostic tests in such patients. METHODS: We searched MEDLINE and EMBASE via OVID, from 1978 until April 2017. We included diagnostic test accuracy studies reporting on the use of fecal and blood tests for the evaluation of adult patients with functional diarrhea, including irritable bowel syndrome. We assessed the risk of bias of included studies using a modified version of the Quality Assessment of Diagnostic Accuracy Studies II, and the certainty in the evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We calculated pooled sensitivity and specificity, and the proportion of patients with true and false positive and negative results. We evaluated the following tests: erythrocyte sedimentation rate, C-reactive protein, fecal lactoferrin, fecal calprotectin, serologic tests for celiac disease, tests for bile acid diarrhea, the commercially available version of anti-cytolethal distending toxin B and anti-vinculin antibodies, and tests for Giardia infection. We did not evaluate breath tests for small intestinal bacterial overgrowth, as they are not part of a standard diarrhea workup. RESULTS: Thirty-eight studies proved eligible to evaluate 1 or more of these tests. Erythrocyte sedimentation rate and C-reactive protein were similar at discriminating organic from functional disease, with sensitivity and specificity, respectively, of 0.54-0.78 and 0.46-0.95 for erythrocyte sedimentation rate and 0.73 and 0.78 for C-reactive protein. Among fecal tests, fecal calprotectin in a range of 50-60 µg/g (pooled sensitivity 0.81; 95% confidence interval [CI], 0.75-0.86; pooled specificity 0.87; 95% CI, 0.78-0.92) and fecal lactoferrin in a range of 4.0-7.25 µg/g (pooled sensitivity 0.79; 95% CI, 0.73-0.84; pooled specificity 0.93; 95%CI 0.63-0.99) presented the lowest proportion of false-negative results (low certainty in the evidence). Among tests for celiac disease, IgA tissue transglutaminase presented the best diagnostic test accuracy (sensitivity range, 0.79-0.99; specificity range, 0.90-0.99) with moderate certainty in the evidence. Among tests for bile acid diarrhea, the 75selenium homotaurocholic acid test performed better than serum fibroblast growth factor 19 and 7α-hydroxy-4-cholesten-3-one, but is not available in the United States. There was insufficient evidence to recommend serologic tests for irritable bowel syndrome at this time. There are several good diagnostic tests for Giardia infection. CONCLUSIONS: Moderate to low certainty in the evidence indicates that available fecal and blood tests may play a role in the diagnostic workup of adult patients with functional diarrhea. At the moment, no tests are available to reliably rule in irritable bowel syndrome.

Development and Validation of the Mucosal Inflammation Noninvasive Index For Pediatric Crohn's Disease.

BACKGROUND & AIMS: Mucosal healing (MH) has become a goal of therapy for Crohn's disease (CD), but frequent endoscopies are not feasible. We aimed to develop and validate a non-invasive index to assess mucosal inflammation in children with CD. METHODS: We collected data from the multi-center prospective ImageKids study, in which children with CD underwent ileocolonoscopy with magnetic resonance enterography. We investigated the association of pediatric CD activity index (PCDAI) items and laboratory test results with the simple endoscopic score for CD (SESCD). We used these data in a blended mathematical judgmental clinimetric approach to develop a weighted categorized index to identify children with CD who have MH, which we called the MINI index. We validated the index using data from 3 independent patient cohorts. The derivation and validation cohorts included 154 and 168 children, respectively (age 14.1 ± 2.5 years and 14.2 ± 3.9 years), of whom 16% and 36% had MH (defined as SESCD<3). RESULTS: In multivariable models, the stooling item of the PCDAI, erythrocyte sedimentation rate, and level of fecal calprotectin were associated with SESCD (all P < .05). We added data on level of C-reactive protein to develop the MINI index. MINI scores below 8 identified children with MH with 88% sensitivity and 85% specificity in the derivation cohort and with 84% sensitivity and 87% specificity in the validation cohorts. Ninety percent of the patients in the validation cohort with scores of 8 or more had active mucosal inflammation, yet 78% of patients with scores below 8 had MH. Scores below 6 increase the positive predictive value to 86%. CONCLUSIONS: We developed an index to non-invasively assess mucosal inflammation in children with CD. This index, identifies children with MH with high sensitivity and specificity. The added benefit of MINI over measurement of fecal calprotectin was small but significant, especially for patients with concentrations of fecal calprotectin from 100 to 599 µg/g. ClinicalTrials.gov no: NCT01881490.

Pediatric Solid Gastric Emptying Scintigraphy: Normative Value Guidelines and Nonstandard Meal Alternatives.

INTRODUCTION: Adult standards for gastric emptying scintigraphy, including the type of meal and range of normative values for percent gastric emptying, are routinely used in pediatric practice, but to date have not been validated. The purpose of this study is to determine whether the use of adult criteria for gastric emptying scintigraphy is valid for children and whether alternative nonstandard meals can also be offered based on these criteria. METHODS: This retrospective study analyzed patients (n = 1,151 total) who underwent solid-phase gastric emptying scintigraphy. Patients were stratified into normal and delayed gastric emptying cohorts based on adult criteria, i.e., with normal gastric emptying defined as ≤10% gastric retention at 4 hours. Patients were further stratified based on the type of meal, namely complete or partial adult standard meals or alternative cheese-based meals. Percent gastric retention values at 1, 2, 3, and 4 hours were compared. RESULTS: The median (95% upper reference limit) percentage gastric retention values for the complete standard meal were 72% (93%) at 1 hour, 39% (65%) at 2 hours, 15% (33%) at 3 hours, and 6% (10 %) at 4 hours. By comparison, the values for cheese-based meals were 60% (87%) at 1 hour, 29% (61%) at 2 hours, 10% (30%) at 3 hours, and 5% (10%) at 4 hours. Consumption of at least 50% of the standard meal yielded similar retention percentages; 68% (89%) at 1 hour, 32% (57%) at 2 hours, 10% (29%) at 3 hours, and 5% (10%) at 4 hours. There were no significant age- or sex-specific differences using the adult criteria. DISCUSSION: The adult normative standards for gastric emptying scintigraphy are applicable for use in the pediatric population. These same standards can be also be applied to nonstandard meal options, including cheese-based alternative meals and partial standard meals.

Artificial Intelligence Applied to Gastrointestinal Diagnostics: A Review.

Artificial intelligence (AI), a discipline encompassed by data science, has seen recent rapid growth in its application to healthcare and beyond, and is now an integral part of daily life. Uses of AI in gastroenterology include the automated detection of disease and differentiation of pathology subtypes and disease severity. Although a majority of AI research in gastroenterology focuses on adult applications, there are a number of pediatric pathologies that could benefit from more research. As new and improved diagnostic tools become available and more information is retrieved from them, AI could provide physicians a method to distill enormous amounts of data into enhanced decision-making and cost saving for children with digestive disorders. This review provides a broad overview of AI and examples of its possible applications in pediatric gastroenterology.

Effect of PNPLA3 polymorphism on diagnostic performance of various noninvasive markers for diagnosing and staging nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.

Older age, symptoms, or anemia: Which factors increase colorectal cancer risk with a positive fecal immunochemical test?

BACKGROUND AND AIM: Fecal immunochemical tests (FIT) are used to screen asymptomatic individuals aged 50-74 years for colorectal cancer (CRC) within the Australian screening program. Gastrointestinal symptoms or iron deficiency anemia (IDA) may also drive primary care physicians to request a FIT. This study aimed to examine factors that may increase neoplasia risk associated with a positive FIT, specifically age, gastrointestinal symptoms, or IDA. METHODS: A retrospective audit was performed on colonoscopies performed in a single hospital in South Australia for a positive FIT (from all referral sources) between 2014 and 2017. Patients aged < 50 years, or who had a colonoscopy in the preceding 5 years, were excluded. A subgroup (n = 198) was evaluated to assess whether age ≥ 75 years, symptoms, or IDA, as well as other demographics, comorbidities, and medications, were associated with risk of neoplasia. Features found to be associated with risk for CRC or high-risk adenoma were examined in the entire cohort using multivariate analysis. RESULTS: Colonoscopies (750/4221, 17.8%) were completed in patients ≥ 50 years for a positive FIT. Of these, 7.6% (n = 57) also had gastrointestinal symptoms, 5.5% (n = 41) IDA, and 13.1% (n = 98) were ≥ 75 years. At colonoscopy, 2.8% (n = 21) were diagnosed with CRC and 23.2% (n = 174) with high-risk adenoma. CRC was more prevalent in ≥ 75 years compared with 50-74 years (7.1% vs 2.1%, P = 0.005), and associated with symptoms (15.8% vs 1.7%, P < 0.001), and IDA (14.6% vs 2.1%, P < 0.001). Multivariate analysis showed that IDA (odds ratio 7.68, P < 0.001) and symptoms (odds ratio 10.37, P < 0.001), but not age, were independent risk factors for CRC. CONCLUSION: The presence of gastrointestinal symptoms or IDA, independent of age, is associated with an increased risk for CRC following a positive FIT.

Prospective comparison of diffusion-weighted magnetic resonance enterography and contrast enhanced computed tomography enterography for the detection of ileocolonic Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic and relapsing course with various status of different segments, and there were no investigations comparing the lesion detection between magnetic resonance (MR) and computed tomography (CT) in term of the severity of CD. We aim to assess the performances of diffusion-weighted MR enterography (DW-MRE) and contrast enhanced CT enterography (CTE) for detecting different grade lesions in ileocolonic CD. METHODS: Forty-one consecutive patients finally diagnosed with ileocolonic CD were included. All the patients prospectively underwent DW-MRE, contrast enhanced CTE, and ileocolonoscopy within 2 weeks. DW-MRE and CTE images were interpreted for the presence or absence of active CD segments by two experienced radiologists independently. Ileocolonic segments (terminal ileum, right colon, transverse colon, left colon, and rectum) were graded as inactive (0-2), mild (3-6), or moderate-severe (≥ 7) by the simplified endoscopic score for CD (SES-CD). Diagnostic efficiencies of DW-MRE and CTE for mild and/or moderate-severe CD segments were calculated and compared, using ileocolonoscopy as reference standard. RESULTS: According to SES-CD, 190 ileocolonic segments from 41 CD patients were scored as 91 inactive, 68 mild, and 31 moderate-severe CD lesions. The sensitivity of DW-MRE for detecting active from inactive segments was higher than that of CTE, and the specificities of them had no significant differences. As for the subgroup analysis, DW-MRE was more sensitive for mild CD lesions than CTE (76.5% vs 60.3%; P = 0.019), while the sensitivities for moderate-severe CD were similar between these two modalities (96.8% for DW-MRE and 93.5% for CTE; P = 1.00). CONCLUSIONS: Both DW-MRE and CTE had comparably excellent performances for moderate-severe CD detection; DW-MRE demonstrated better sensitivity in mild lesions compared with CTE and could be more suitable for the diagnosis of mild CD.